Older Agents to Manage ASCVD and Hypercholesterolemia

Experts discuss use of older agents to control atherosclerotic cardiovascular disease (ASCVD) and hypercholesterolemia in certain patient populations.

Yehuda Handelsman, MD: Let's move forward. Another drug that we have available is bile acid sequestrants, which have been used since the 1990s. They lost a lot of their luster because other drugs like statins became much more popular. Colesevelam is a recent—20 years, is still recent— drug that we use. It's better than the older one as it is much more tolerated. It also has impact on glucose and is approved to reduce glucose, but it’s not used as much because 6 large pills are not fun to drink; to drink it now you can put it in a shake or something. It's modest, but if they're truly statin intolerant, they do a combination of orals, and they don't want an injectable, it's a nice addition that we have. Do you want to touch on niacin? People don't like to use it.

Erin D. Michos, MD, MHS: Yeah, niacin's fallen out of favor. It lowers LDL [low-density lipoproteins] and lipoprotein-a, and it raises HDL [high-density lipoprotein], but it has not been shown to reduce major adverse cardiovascular events on top of a statin, and it has a lot of side effects, making it difficult to tolerate. In a trial, there were increased rates of mortality; although it wasn't statistically significant, there was this concern signal for harm. Because of that and because we have now so many other agents to lower LDL, it has fallen out of favor.

Handelsman: Is anybody else still using it?

Christie Ballantyne, MD: I have patients that I still have on niacin because they've responded well to it, but it's way down the list now. It's something when everything else has failed you would consider it, but in general, if they can't tolerate the other therapies, there's no way they can tolerate niacin.

Handelsman: I still use it here and there because of what Erin said, it can get some added impact on LDL, triglyceride, and…but it's really come out of it. Let's look at some other drugs. Fenofibrate is also approved for LDL reduction beyond triglyceride. We tend to forget it. Do you like fenofibrate, Paul?

Paul S. Jellinger, MD, MACE: I used to like fenofibrate, I'm fond of them, but I wouldn't say I like them. I'm OK with them. Fenofibrates are triglyceride-lowering agents that are effective, they're probably our best triglyceride-lowering agents, even more potent than high dose omega fish oils. They have the reputation of not having convincing evidence that there will be reduced cardiovascular outcomes with all the trials that have been done using them. When you look at all 5 major fenofibrate trials on secondary analysis, patients who had high triglycerides and low HDL had a cardiac outcome benefit, which is a statistically significant reduction in outcomes. However, it was only in those patients with metabolic syndrome, where triglycerides were elevated, and HDL was low. The subgroup analysis is positive but the primary outcome is not. We're not sure what fibrates really do. I use them when I need to lower triglycerides in conjunction with omega fish oils as a very powerful combination. I was using it until omega fish oils come out with the powerful REDUCE-IT study, and with those patients in the secondary analysis, high triglycerides, low HDL, to reduce cardiovascular outcomes.

Handelsman: I still believe in the lower everything, the better, so I like triglycerides to be low. Especially because we know that starting at 70, 80 of triglycerides is like moving the size of LDL from the larger to the smaller dents; by 135, that's usually where the change was done by studies by…at the time. We would often use it, and I'll have you, Matt, discuss it soon. In the REDUCE-IT, 135 was the trigger for risk, if a patient had 320 and you gave them a fish oil, omega 3 or the other fish oil, and it brings them down to 260, are they not going to still be at-risk long term? We don't know that of course, but the potential may be there.

Michos: In population-based studies like ERIC, the risk for increased cardiovascular events starts at 50-200, and then once you get above a certain level of triglycerides, the risk flattens out; risk starts increasing in levels that we consider normal triglycerides.

Jellinger: Absolutely.

Michos: There is still one large cardiovascular outcome trial of a fibrate ongoing, Pemafibrate, the trial's called PROMINENT. We haven't completely abandoned the idea of fibrates for cardiovascular disease prevention. I'm looking forward to seeing the results of that trial.

Matthew J. Budoff, MD: To your point, that's studying the population that Paul described, to get into that trial you have to be high triglycerides, low HDL. That will study those subgroups that you described.

Ballantyne: Although fenofibrate alone can lower LDL, if you add it to a high-intensity statin, it does not give further LDL reduction. In the label before, they took that out of it. We did the studies with fenofibric acid, which was very disappointing in that, for the patient not on statin, you get LDL but once you're on a high-intensity statin…

Handelsman: Also the triglyceride is not high, a high triglyceride it will not reduce the LDL.

Ballantyne: Yeah, it does not. Pemafibrate had some recent data that didn't look like it did much for…on top of that.

Transcript Edited for Clarity

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